From Cohorts to Molecules: Adverse Impacts of Endocrine Disrupting Mixtures
| Autor: | Wieland Kiess, Giuseppe D'Agostino, Eewa Nånberg, Sebastiano Trattaro, Åke Bergman, Rantakkoko P, Chris Gennings, Leemans M, Carl G. Bornehag, Matteo Zanella, Filip Rendel, Pauliina Damdimopoulou, Vesna Munic Kos, Giuseppe Testa, Demeneix B, Cavallo F, Efthymia Kitraki, Fini J, Raul Bardini Bressan, Chorev Ne, Joachim Sturve, Joëlle Rüegg, Birgitta E. Sundström, Steven M. Pollard, Christina Rudén, Nicolò Caporale, Birgersson L, Pierre-Luc Germain, Alejandro Lopez Tobon, Borbély G, Jönsson M, Hannu Kiviranta, Olle Söder, Lazzarin M, Mattias Öberg |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0303 health sciences
education.field_of_study biology ved/biology Offspring Population ved/biology.organism_classification_rank.species Gene regulatory network Early pregnancy factor Computational biology Health outcomes 3. Good health Toxicology 03 medical and health sciences 0302 clinical medicine biology.protein Endocrine system Identification (biology) education Model organism 030217 neurology & neurosurgery 030304 developmental biology |
| DOI: | 10.1101/206664 |
| Popis: | Convergent evidence associates endocrine disrupting chemicals (EDCs) with major, increasingly-prevalent human disorders. Regulation requires elucidation of EDC-triggered molecular events causally linked to adverse health outcomes, but two factors limit their identification. First, experiments frequently use individual chemicals, whereas real life entails simultaneous exposure to multiple EDCs. Second, population-based and experimental studies are seldom integrated. This drawback was exacerbated until recently by lack of physiopathologically meaningful human experimental systems that link epidemiological data with results from model organisms.We developed a novel approach, integrating epidemiological with experimental evidence. Starting from 1,874 mother-child pairs we identified mixtures of chemicals, measured during early pregnancy, associated with language delay or low-birth weight in offspring. These mixtures were then tested on multiple complementary in vitro and in vivo models. We demonstrate that each EDC mixture, at levels found in pregnant women, disrupts hormone-regulated and disease-relevant gene regulatory networks at both the cellular and organismal scale. |
| Databáze: | OpenAIRE |
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